Microbiology Nuts & Bolts: Occupational Health

1. Microbiology Nuts & Bolts: Occupational Health Dr David Garner Consultant Microbiologist Frimley Park Hospital NHS Foundation Trust

2. Aims & Objectives To be aware of the rising threat of antibiotic resistance and how this will impact patient care To look at how “Nuts & Bolts” came about

3. Mary 55 year old nurse Referred by supportive ward manager Been diagnosed by own GP with recurrent UTIs Absence from work due to infection is a problem On examination Temperature 38 oC Abdominal pain Diagnosed with probable UTI and started on Nitrofurantoin (recent course of Trimethoprim) Mid-stream urine (MSU) sent to the laboratory

4. How to interpret a urine result? Urine dipstick Poor PPV, Good NPV Microscopy White blood cells, red blood cells, epithelial cells Culture result Is the organism consistent with the clinical picture?

5. Microscopy of urine White blood cells >100 x106/L definitely significant >10 x106/L significant if properly taken MSU (rare!) Red Blood Cells Poor correlation with UTI, used by urologist and renal physicians Epithelial cells Indicator of contact with, and therefore contamination from, the perineum

6. Culture: classification of bacteria

7. Culture: how is urine processed? Day 1 Automated Microscopy If values not significant reported as negative If values significant or specific patient group cultured with direct sensitivities Day 2 Reported with identification and sensitivities Patient groups always cultured Cancer and haematology Pregnant Urology Children < 5 years old

8. Back to Mary… Review of MSU result Microscopy >100 x106/L WBC, no epithelial cells Culture E. coli ESBL positive Resistant to Amoxicillin, Co-amoxiclav, Trimethoprim, Nitrofurantoin, Cephradine, Ciprofloxacin What is an ESBL?

9. Caution: Extended Spectrum Beta-lactamase Enzyme excreted into periplasmic space which inactivates antimicrobials by cleaving the b-lactam bond. Cause resistance to almost all b-lactams including 3rd-generation cephalosporins Associated with multiple antibiotic resistances Can be chromosome, plasmid or transposon encoded Can be constitutive or inducible Ideally patients with ESBLs should be managed in side-rooms with contact precautions

10. Transfer of antibiotic resistance

11. Caution: Extended Spectrum Beta-lactamase Source: European Centre for Disease Prevention and Control Antimicrobial resistance surveillance in Europe 2015

12. Caution: Extended Spectrum Beta-lactamase Carbapenems are the treatment of choice Some advocate Beta-lactamase inhibitor combinations (BLI) e.g. Co-amoxiclav, Piptazobactam Insufficient evidence Systematic review & metanalysis JAC 2012; 67: 2793-2803 Carbapenems > non-BLI BLI not< carbapenems BLI not > non BLI How can BLI = carbapenems?! Personally use carbapenems for serious infections caused by ESBL positive bacteria

13. But what about carbapenemases? • Carbapenems are the broadest spectrum antibiotics available • Ertapenem • Meropenem • Imipenem • Doripenem • Carbapenemases are Beta-lactamase enzymes which hydrolyse carbapenems • Confer resistance to ALL Beta-lactam antibiotics • Often transferable on mobile genetic element e.g. plasmid

14. The “Big Five”: • Klebsiella pneumoniae carbapenemase (KPC) • Verona integron-encoded metallo-beta-lactamase (VIM & IMP) • New Delhi metallo-beta-lactamase (NDM) • Oxacillin Carbapenemases (OXA) • Should be considered in all patients transferred to UK from abroad • Recent guidance supports screening and infection control precautions for these patients

15. KPC

16. VIM & IMP

17. NDM

18. OXA-48

19. Investigation • Difficult • No perfect single method for detecting • Treatment • Colistin PLUS carbapenem • Colistin PLUS Tigecycline • Colistin PLUS aminoglycoside (very nephrotoxic) No orals!!!

20. Why worry? • Overreliance on single classes of antibiotics is a selective pressure that drives resistance • There are no new antibiotics for Gram-negative bacteria in the pipeline • We are approaching the Post-antibiotic era (only 100 years after the first antimicrobial was discovered – Salvarsan for syphilis 1911)

21. ESBLs in Europe 2002 2012 European Centre for Disease Prevention & Control

22. Carbapenemases? 2012 2024? European Centre for Disease Prevention & Control

23. The Future?

24. The Present?

25. Mary Treated with PO Fosfomycin 3g stat UTI settled Conclusion: not recurrent UTIs but failure to eradicate original UTI due to antibiotic resistance Warning – Mary is now colonised with Antibiotic-resistant E. coli so future UTIs are likely to be resistant as well (it is part of her normal flora!)

26. Any Questions?

27. Microbiology Nuts & Bolts

28. First steps Assemble you team: • Author = Microbiology expert • Editor = Non-expert in Microbiology (but understands healthcare = Jenny (Wife and ex-physiotherapist!) • Advisors = Prof. Hoops (one of the Cat Club!!!)

29. First steps • Have a theme and stick to it • Be consistent • Think about the target • Be brave!

30. Stop talking about it…

31. Createspace

32. Marketing 4 Microbiologists • The website • Teaching • Amazon reviews (give away copies?) • Peer reviews • Blog – The Bug Blog (MNB & Doctors.net) • Facebook • Unforeseen outcomes…

33. The website

34. Teaching • Medical Students • Foundation Year • Core training • GPs • Pharmacists • and Occupational Health Consultants!

35. Amazon

36. Peer reviews • Royal College of Pathologists  • A well-written book...concise, well set out and easy to use. It contains a wealth of useful information and is a valuable resource • Royal College of Physicians • This book delivers a uniquely relevant and accessible take on microbiology and does an excellent job of bridging the gap between the dry lists of pathogens learnt at medical school and the clinical reality of infection • British Society for Antimicrobial Chemotherapy • This book provides an impressively broad coverage of microbiology in theory and practice and I can see uses for it for students, junior doctors and general practitioners • Royal Pharmaceutical Society • Pocket guide to all things infection related packs a vast amount of information into a small space, and would be a useful back-up or portable revision aid for any pharmacist dealing with infection • Institute of Biomedical Science • A comprehensive yet concise book that would be useful to any healthcare professional managing patients with infections • Hospital Infection Society • A very good pocket guide covering the basics of microbiology… it forms a good base of knowledge for specialist trainees

37. The Bug Blog A blog a week is very hard work!

38. Facebook

39. Unforeseen outcomes… • Poldark’s Putrid Throat = Number 1 hit on Google – global emails • Interpretation of death certificates for history buffs • The Bug Blog • Requests to act as medical expert in medicolegal cases • Mentorship for FRCPath in Pakistan • Teaching • St. George’s Medical School award

40. Microbiology Nuts & Bolts • Further reading: • Microbiology Nuts & Bolts by Dr David Garner • www.microbiologynutsandbolts.co.uk • Facebook page for Microbiology Nuts & Bolts Available to buy on